This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Through previous collaborations with scientists at the Biocurrents Research Center, we demonstrated the role of pH in mediating the toxicity of alloxan in pancreatic beta islets. Self-referencing oxygen sensing electrodes have proven to be an ideal way to study isolated islet function (oxygen consumption) in real time. It is well recognized that oxygen consumption by islets is strongly correlated with insulin release. Alloxan stability and thus toxicity is affected by pH. We have established that presence of glucose dampens alloxan toxicity in pancreatic islets. This effect is due to the intracellular alkalinization, caused by glucose metabolism. We propose to expand this collaboration by studying the role of oxidative stress in beta islet function. Previous studies have demonstrated that oxidative stress can positively and negatively impact beta islet function. While streptozotocin-induced islet toxicity can be blocked by catalase and superoxide dismutase expression, hydrogen peroxide also seems to play an important role in signaling in response to glucose stimulation. The mechanisms by which islets differentiate between harmful and helpful oxidative stress are not clear.